The OncFive: Top Oncology Articles for the Week of 10/25

Welcome to OncLive®’s OncFive!

Every week, we bring you a quick roundup of the 5 top stories from the world of oncology—ranging from pivotal regulatory decisions to key pipeline updates to expert insights on breakthroughs that are moving the needle in cancer care. This resource is designed to keep you informed on the latest updates in the space, in just a matter of minutes.

Here’s what you may have missed this week:

Ivonescimab Plus Chemotherapy Represents a New SOC in First-Line Biliary Tract Cancer

Ivonescimab (SMT112; AK112) plus gemcitabine and cisplatin improved overall survival (OS) vs durvalumab (Imfinzi) plus the same chemotherapy as first-line treatment for patients with advanced biliary tract cancer (BTC) in the randomized, double-blind phase 3 HARMONi-GI1 trial (NCT06591520), according to data presented at the 2026 ESMO Congress. At a median follow-up of 14.3 months, the median OS was 14.9 months (95% CI, 12.9-not evaluable) with ivonescimab (n = 340) vs 12.1 months (95% CI, 11.0-13.4) with durvalumab (n = 342; hazard ratio [HR], 0.75; 95% CI, 0.61-0.92; 1-sided P = .0031), and the 18-month OS rates were 44.0% vs 32.5%, respectively. Ivonescimab also improved both key secondary end points, with a median progression-free survival (PFS) of 8.4 months vs 5.8 months (HR, 0.61; 95% CI, 0.51-0.72; 1-sided P < .0001) and an objective response rate (ORR) of 53.8% vs 32.5% (P < .0001); the OS HR was 0.63 (95% CI, 0.48-0.83) among patients with intrahepatic cholangiocarcinoma. Grade 3/4 treatment-emergent adverse effects (TEAEs) occurred in 82.0% vs 72.3% of patients, TEAEs led to discontinuation in 3.5% vs 5.6%, and toxicities potentially associated with VEGF inhibition, including proteinuria (32.2% vs 11.8%) and hypertension (15.0% vs 2.4%), were more frequent with ivonescimab. Ivonescimab plus chemotherapy will be further evaluated in the United States in the phase 2/3 EA2251 trial (NCT07765433), which will compare it with pembrolizumab (Keytruda) or durvalumab plus chemotherapy, with OS as the primary end point.

FDA Approves Talazoparib Plus Enzalutamide for Metastatic, HRR+ APMN/S Prostate Cancer

The FDA approved talazoparib (Talzenna) plus enzalutamide (Xtandi) for adult patients with metastatic androgen pathway modulation–naive or –sensitive (mAPM/S) prostate cancer with homologous recombination repair (HRR) gene mutations, as detected by an FDA-authorized test. The decision was supported by the randomized, double-blind phase 3 TALAPRO-3 trial (NCT04821622; n = 599), in which talazoparib plus enzalutamide improved radiographic PFS (rPFS) vs placebo plus enzalutamide (HR, 0.48; 95% CI, 0.36-0.65; P < .0001), with a median rPFS that was not reached vs 45.8 months (95% CI, 37.7-not reached), respectively. The 36-month rPFS rates were 76.6% vs 56.2%, and at the interim OS analysis, the median OS was not reached in either arm, with 36-month OS rates of 77.8% vs 71.6%. The combination also prolonged time to prostate-specific antigen progression (HR, 0.513; 95% CI, 0.370-0.712; P < .0001), and grade 3 or 4 TEAEs occurred in 79% vs 41% of patients, driven largely by grade 3 or 4 anemia (51% vs 3%). Talazoparib is recommended at 0.5 mg orally once daily with enzalutamide until disease progression or unacceptable toxicity, and FoundationOne CDx and FoundationOne Liquid CDx serve as the companion diagnostics for the indication.

Petosemtamab Plus Pembrolizumab Hits Phase 3 OS, ORR Primary End Points in PD-L1+ R/M HNSCC

The addition of petosemtamab (MCLA-158), an investigational EGFR- and LGR5-directed bispecific antibody, to pembrolizumab significantly improved OS and ORR vs pembrolizumab monotherapy as first-line treatment for patients with PD-L1–positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), meeting both primary end points of the phase 3 LiGeR-HN1 trial (NCT06525220). At the first interim analysis, the combination reduced the risk of death by 50% vs pembrolizumab alone (HR, 0.5; 95% CI, 0.37-0.67; P < .0001), and the ORR odds ratio was 3.17 (95% CI, 2.06-4.89; P < .0001), according to topline findings announced by Genmab. The OS and ORR benefits were observed irrespective of human papillomavirus status, and the combination was generally well tolerated, with a safety profile consistent with that of each agent individually and no new safety signals. The open-label trial enrolled patients with a PD-L1 combined positive score of 1 or higher who had received no prior systemic therapy in the recurrent or metastatic setting, and secondary end points include PFS, duration of response, clinical benefit rate, and time to response. Data from LiGeR-HN1 will be submitted for presentation at a future medical meeting and shared with global health authorities.

Divarasib Improves Survival and Paves Way for New SOC in Pretreated KRAS G12C–Mutated NSCLC

Divarasib improved PFS and OS vs sotorasib (Lumakras) or adagrasib (Krazati) in patients with previously treated, locally advanced or metastatic KRAS G12C–mutated non–small cell lung cancer (NSCLC) in the phase 3 Krascendo 1 trial (NCT06497556), according to primary findings presented at the 2026 ESMO Congress and published in the New England Journal of Medicine. At a median follow-up of 14.3 months, the median PFS per blinded independent central review was 9.8 months (95% CI, 8.1-12.9) with divarasib (n = 167) vs 5.7 months (95% CI, 4.2-6.8) with sotorasib or adagrasib (n = 171; HR, 0.58; 95% CI, 0.44-0.76; P < .0001). At the first interim OS analysis, the median OS was 17.7 months (95% CI, 16.3-not evaluable) vs 12.0 months (95% CI, 10.0-15.2), respectively (HR, 0.56; 95% CI, 0.41-0.78; P = .0005), and the confirmed ORR was 58% vs 32%, with a median duration of response of 11.9 vs 6.9 months. Although diarrhea (66% vs 38%), nausea (53% vs 20%), and vomiting (39% vs 8%) were more common with divarasib, grade 3/4 treatment-related adverse effects (TRAEs) occurred in 24.6% vs 34.5% of patients and TRAEs led to discontinuation in 4.8% vs 11.7%. Divarasib is also being evaluated with pembrolizumab in the first-line phase 3 Krascendo 2 trial (NCT06793215) and in the adjuvant setting in the phase 3 Krascendo 3 trial (NCT07541170).

KEYNOTE-C93 Shows PFS Benefit With First-Line Pembrolizumab Monotherapy in dMMR Endometrial Cancer

First-line pembrolizumab monotherapy improved PFS vs carboplatin plus paclitaxel in patients with mismatch repair–deficient (dMMR) advanced or recurrent endometrial cancer in the phase 3 KEYNOTE-C93/GOG-3064/ENGOT-en15 trial (NCT05173987), according to data presented at the 2026 ESMO Congress and published in The Lancet. At a median follow-up of 36.7 months, the median PFS per blinded independent central review was 38.2 months (95% CI, 17.9-not reached) with pembrolizumab (n = 149) vs 8.4 months (95% CI, 6.8-10.4) with chemotherapy (n = 150; HR, 0.57; 95% CI, 0.42-0.79; P = .0002), and the 36-month PFS rates were 52.8% vs 30.0%, respectively. OS, the dual primary end point, numerically favored pembrolizumab but did not meet the prespecified criterion for statistical significance at this interim analysis (HR, 0.77; 95% CI, 0.52-1.15; P = .1000), with 36-month OS rates of 70.7% vs 62.0%; notably, 85.2% of patients in the chemotherapy arm with progression received subsequent immunotherapy. The ORR was 64.1% vs 62.1%, but the rate of duration of response of 36 months or longer was 70.7% vs 40.0%, and grade 3 or higher TRAEs occurred in 18.1% vs 50.7% of patients. The investigators noted that the trial did not compare pembrolizumab with chemotherapy plus immunotherapy, the current first-line standard of care, but concluded that pembrolizumab monotherapy may broaden first-line treatment choice for certain patients with dMMR disease.